Organophosphorus insecticides derived from mono- and di-oxo benzoxazines



United States Patent 3,467,655 ORGANOPHOSPHORUS INSECTICIDES DERIVED FROM MONO- AND DI-OXO BENZOXAZINES Michio Nakauishi, Oita, and Atsushi Tsuda and Shuji Iuamasu, Fukuoka, Japan, assignors to Yoshitomi }harmaceutical Industries, Ltd., Higashi-ku, Osaka,

apan No Drawing. Filed Apr. 5, 1967, Ser. No. 628,560 Claims priority, application Japan, Apr. 5, 1966, 41/21,598; Nov. 15, 1966, 41/75,062; Nov. 16, 1966, 41/75,600

Int. Cl. C07f 9/08, 9/40; A01n 9/36 US. Cl. 260244 13 Claims ABSTRACT OF THE DISCLOSURE Organophosphorus compounds of the formula wherein X is H, halogen or alkyl with a maximum of 4 carbon atoms, Z is carbonyl, alkylidene with a maximum of 6 carbon atoms, benzylidene or cyclohexylidene, =Y is =0 or :8, Y is O-- or --CH Y in which Y is O-- or S-- directly bound to OR -P a... R is methyl or ethyl, and R is methoxy, ethoxy or phenyl,

are effective insecticides and miticides with low toxicity to to warrnblooded animals and of low residual toxicity.

This invention relates to organophosphorus compounds and insecticidal and miticidal compositions containing the same.

The organophosphorus compounds are of the formula NY P wherein R is methyl or ethyl, and R is methoxy, ethoxy or phenyl.

In the above-mentioned formula the halogen is exemplified by Cl, Br, etc., the alkyl of a maximum of 4 carbon atoms by CH C H Il-C3H7, n-C H sec-C.,H, and

tert-C H etc., and the alkylidene of a maximum of 6 carice and =CH (CH CH etc. When Y is CH Y Compound I has the formula X i l l R1 N-CH2Y"-P The present Compounds I are prepared either (i) by reacting a compound of the formula wherein M is H or alkali metal (e.g. sodium, potassium, etc.) and X, Z and Y are as above defined, with a compound of the formula hal-P wherein hal is halogen (e.g. chlorine, bromine, etc.) and R R and Y are as above defined, or (ii) by reacting a compound of the formula Y OR hal

wherein M is H or alkali metal, and R R Y and Y are as above defined. Either reaction is carred out in a solvent (e.g. methanol, ethanol, acetone, dimethylformamide) at 10-l00 C., preferably at room temperature (2030 C.) or with a little heating or cooling, for about 0.5 to several hours. When M is H, the presence of a basic substance (e.g. potassium or sodium hydroxide or carbonate, triethylamine, pyridine) is advantageous.

Typical but non-limitative examples of the preparation of the compounds of the invention are as follows. Parts by weight bear the same relationship to parts by volume as do grams to milliliters.

Example 1 6.1 parts by Weight of 0,0-diethyl chlorothiophosphate is stirred dropwise into a mixture of 5.4 parts by weight of 3-hydroxy-2,4-dioxo-2,3 dihydro-4H-1,3-benzoxazine, 4 parts by weight of pyridine and 45 parts by volume of dimethylformamide. The solution is stirred at room temperature for 3 hours, and then poured into 200 parts by volume of iced water. The precipitate formed is separated and recrystallized from ethanol to give 8 parts by weight of colorless crystals of 0,0-diethyl O-(2,4-dioxo-2,3-dihydro-4H- 1,3-benzoxazine-3-yl)phosphorothioate with a melting point of 107-108.5 C.

An-alysis.--Calculated for C H O NSP: C, 43.50; H, 4.26; N, 4.23. Found: C, 43.82; H, 4.28; N, 4.18

Example 2 1.95 parts by weight of potassium 0,0-dimethyl thiophosphate is added portionwise to a stirred solution of A solution of 2.2 parts by weight of 3-chloroniethyl-6- methyl-2,4-dioxo-2,3-dihydro-4H-1,3-benzoxazine and 2.5 parts by weight of potassium 0,0-diethylthiophsphate in 25 parts by volume of acetone is heated under reflux for an hour, cooled, filtered to remove precipitate (KCl), concentrated, dissolved in 50 parts by volume of benzene, washed with two portions of water, dried over anhydrous magnesium sulfate and concentrated to give 2.3 parts by 2,4 dioxo 2,3 dihydro 4H 1,3 benzoxazin 3 yl) methyl] phosphorothioate, n =1.5364.

AnaIysis.-Calculated for C H O NSPz C, 46.79; H, 5.05; N, 3.90. Found: C, 46.43; H, 4.89; N, 3.95.

Example 4 3.2 parts by weight of 0,0-dimethyl chlorothiophosphate is added to a stirred solution of 3.86 parts by weight of 2,3 dihydro 3 hydroxy 2 ethyl 4 oxo 4H. 1,3- benzoxazine in parts by volume of methanol containing 1.35 g. of potassium hydroxide. The mixture is stirred for 2 hours at room temperature, the methanol then distilled off, chloroform added to the residue, and the solution washed with two portions of water, dried, and concentrated. The residue is recrystallized from ethanol to give 3.6 parts by weight of 0,0-dimethyl O-(2-ethyl-4-oxo-2,3- dihydro-4H-1,3-benzoxazine-3-yl)phosphorothioate melting at 7879 C.

These and other organophosphorus compounds which weight of a transparent oil of 0,0-diethyl O-[(6-methyl- 20 can thus be obtained are listed in the following table:

TABLE :00 O- --S- C2H5 O C1115 =CO O -S CH; OCHx =CO CH2O S- C2H5 O C2H5 =CHCgII O --S- CH3 0 CH1 =CO O O- C2H5 O C 11 White crystals, M.P. Bil-90 C. (diisopropyl ether) =C O CH:O S C211 O C311 White needles, M. P. 79-82 C. ((11150- ropyl ether-ethanol (20: 1)). =CO CH2S S- OH; OCHa W 11:16 gvux, M.P. 35-40 C. (petroleum et er =CO CH2S- S CZIIS OCQH; White needles, M.P. 57 C. (ethanol). =CO CH20- S-- CH OCH; White needles, M.P. 120-125 C. (dilsopro yl ether-ethanol (20:1)). =00 CH:S- -S C 11 OCzHs Cologess needles, M.P. 8284 C. (ethano =CO CH2S S- CH OCH; Semigransparent crystals, M.P. 5859 C.

(et anol C O CHzS- S- C2115 O C211 White amtfirphous powder, M.P. 7T80 C.

et iano =CO -CH2O- S OgHs OCBHs White needles, M.P. 103105.5 C.

(ethanol). =C 0 CH2S -S CH3 0 CH Crystzlals, M.P. 40-45" C. (aqueous met iau =00 CH:S S- CZIIS 0 C Hs Crystals, M.P. 77 C. (ethanol). 6-C(CH3) =0 0 --O- S- CQH5 0 (32H Pale yellow oil, n -Lffll. 17 G-CH; =C O O- S- CgHs O 02H; Transparent 01]. 1S fi-CH; =00 O- -S- CH OCH whir needles, M.P. 92-93.5 C. (ethano 19 6-Br =C O O -0 0211 0 0211 White amo hous powder, M.P.

C. (et iunol). 2O S-CH; =C 0 -0 i C2115 O C211 Colorless scales, M.P. 55-58 C. (ethanol). .21 8-0113 =00 O C11; OCII; Cololrl)ess scales, M.P. 124-128" C. (ethano J3 ll =Cl1C1l(C1l;): S- CII; OCH; White crystals, M.P. 4143.1? C. (petroleum benzine). 2.; 11 =CHCI1(CH;)2 O S- C II5 0 C211 Pale brown oil. .21 ll =C(CH:)4CH2 O- -S CH3 0011 White crystals, M.P. 64(i6 C. (petroleum benzine).

25 H =C (CH2)4CH2 0- -S-- Call 0 C911 White crystals, MP. 7881 C. (petroleum benzine).

2o H =CH -O S- CH3 OCHa Whits crystals, M.P. 110-112" C. (etha- :CIIQ O S- C211 O CaH White crystals, M.P. 45-46 C. (ethanol).

=CHCII; -O- CH; O CH; WhitIe crystals, M.P. 82.584 C. (ethano =CHCHa O- C2H5 OCzHs Whit?) crystals, M.P. 80-8133" C. (ethano =CHC H --O- C2115 0 C211 Pale yellowish brown oil. =CHC2H5 O 01H; 0 0211 Pale brown oil, n =1.5080. =CH(CH2)2CI'I3 O CH3 0 CH3 Pale yellow oil, nD =1.5420. CH(CH2)2CH3 O- CeHs 0 0211 Pale yellow oil, 7Z =1.528O. CHCH(CH3): O CzH O CzHs White crystals, M.P. 47-49" C. (peli'oleum benzine). =CH(CII2)3CI'I3 O- C211 0 0211 Pale brown 011, n, =1.527'8. =CH(CI-IE);CH; O- CH; 0 CH3 Pale brown oil, n =l.5342. =CH(CH2)4CH3 O- 011 1 0 CgH Pale brown 011, m =1.5237. =CH(CHg)4CH --O CzHs O CQH5 Pale brown 011, nD =1.5029. =C (CII2)4CH2 O- CgHs 0 Calls Pale red oil, nD =1.5l83.

=C(CH3)2 O- -S- CH3 0 C11; Pale yellowish brown oil. 11;)":15470. =C(C 3 -O -S C O CzHs Pale brown oil, n =1.5322. =C(CH --O-- O C211 OC'2H5 Pale reddish brown 01'], 11 =l.5iU1. =C(CH3)(C:H5) O- S- CH1 0 CH3 Pale brown oil, 1L =L5475. =0 (CH3)(C2H -O S C211 O C 115 Pale brown oil, n 1.5333. =C (CH1) (C2Hs) -O O- C:H O CzHs Pale brown oil, n =1.6094. =on- -o- -s- (3211; Q Crystals, M.P. sass" o.

The compound included in parenthesis is, throughout this table, the solvent used for recrystallization.

The compound of Example 5 is diethyl(2,4-dioxo-2,3- dihydro-4H-1,3-benzoxazin-3-yl) phosphate.

Thecompound of Example 7 is 0,0-dimethy1 S-[(2,4- dioxo-2,3-dihydro-4H-1,3-benzoxazin-3-yl)-methyl] phosphorodithioate.

The compound of Example 8 is 0,0-diethyl S-[(2,4-dioxo-2,3-dihydro-4H-1,3-benzoxaZin-3-yl) methyl] phosphorodithioate.

The, compound of Example 13 is 0,0-diethyl O-[(6- bromo-2,4-dioxo-2,3-dihydro-4H-1,3-benzoxazin 3 yl) methyl] phosphorothioate.

The compound of Example 20 is 0,0-diethyl O-(8- methyl-2,4-dioxo-2,3-dihydro-4H-l,3-benzoxazin 3 yl) phosphorothioate.

The, compound of Example 22 is 0,0-dimethyl O-(2- isopropyl-4-oxo-2,3-dihydro-4H-1,3 benzoxazin 3 yl) phosphorothioate.

The compound of Example 27 is 0,0diethyl O-(2- pheny1-4.-oxo-2,3-dihydro-4H-l,3-benzoxazin-3 yl) phosphorothioate.

The compound of Example 29 is 0,0-diethyl O-(2- methyl-4 oxo-2,3-dihydro-4H-1,3-benzoxazin-3 yl) phosphorothioate.

The compound of Example 30 is 0,0-diethyl O-(2- ethyl-4-oxo-2,3-dihydro-4H-1,3-benzoxazin 3 yl) phosphorothioate.

The compound of Example 23 is 0,0-diethyl O-(2-isopropyl-4-oxo-2,3-dihydro-4H-1,3-benzoxazin-3 yl) phosphorothioate.

The compound of Example 35 is 0,0-diethyl O-(Z-butyl-4-oxo-2,3-dihydro-4H-1,3-benzoxazin-3-yl) phosphorothioate.

The Compounds I are insecticides and miticides with low order of toxicity to warm-blooded animals. They can effectively kill various agricultural and household pests such as .fiies (e.g., housefly), mosquitoes (e.g., Culex species), weevils (e.g. Adzuki bean weevil), cockroaches (e.g. German cockroach), green rice leafhoppers, rice stem borer, mites and aphids. Although they are stable in anhydrous state, they are relatively rapidly hydrolyzed in the presence of water into still less toxic or practicaly non-toxic substances after killing the pests. Therefore they can be used safely and without anxiety of residual problems. Moreover the odor characteristic to organophosphorus insecticides is slight or not perceptible, and therefore the baits containing them may be in particular favorable and preferable, e.g., to cockroaches. Furthermore manyof them are solids and this fact is advantageous in their handling.

Test 1 Median lethal dose (LD against the housefly Musca domestica vicina (Takatsuki strain) was determined from mortalities after 24 hours by topical application method using acetone soutions as follows:

Compound of Example- LD ('y/fiy) One milliliter of 0.5% acetone solution of each of the compounds of Examples 3, 6, 7, 8, 9 and 16, spread on the bottom of a petri dish (9 cm. diameter) and air-dried, killed of 10 individuals of the German cockroach Blatelia germam'ca Linn brought into contact with the compound on the bottom in 24 hours.

Test 3 Compounds of Examples 7, 20 and 30 each dissolved in acetone and topically applied to 10 rice stem borers (Chi/0 suppressalis Walker) at the dose of 50'y/borer, kiled 100% of the borers in 24 hours.

Test 4 Leaves of the kidney bean infested with the Kanzawa spider mite T etranychus kanzawai Kishida were sprayed with a 0.05% acetone solution of the compound of Examples l, 5, 6, 7, 8, 10, 12 or 13. The leaves were kept 2 days at 28 C. and then microscopic observation was made. In each case the mortality of the mite was 100%.

Test 5 The oral LD in mice was determined as follows:

Compound of Example- LD (mg./ kg.)

5 104 23 2900 27 1850 Parathion 5.2

Test 6 The rate of hydrolysis was evaluated by measuring the electric conductivity change of the saturated solution of the test compound prepared by dissolving 1-00 mg. of the compound in a small amount of methanol, adding a surface active agent and diluting the solution with 100 ml. of water. The hydrolysis supposedly proceeds as follows:

and therefore the conductivity increase (K, mho./ hr.) is a measure of the hydrolysis rate. Results were as follows:

Compound of Example K(rnho./hr.)

7 Compound of Example K(mho./hr.) 28 1.29

40 0.59 Parathion 0.13

Insecticidal and miticidal compositions are prepared by mixing at least one of the organophosphorus compounds of the invention such as above described with a suitable carrier therefor in a per se known manner. The carrier is, for example, liquid such as benzene, toluene, xylene, acetone, methyl, isobutyl ketone, dimethylformamide, solvent naphtha, methylnaphthalene, kerosene; soFid such as talc, clay, bentonite, kaolin, diatomaceous earth, fish meal, or a mixture or these. The compositions may contain a surface active agent such as polyoxyethylene alkyl (or alkylphenyl) ether or polyoxyethylene-sorbitan fatty acid ester, or other adjuvants. Thus, the compositions may take the form of emulsions or emulsifiable concentrates, wettable powders, dusts, solutions, or baits. The compositions may also contain other insecticides and miticides as well as fungicides, herbicides, fertilizers, etc.

Examples of formulations are as follows (parts being by weight) Example 47 (dust): Parts Any Compound I 2 Clay or talc 98 Example 48 (emulsifiable concentrate):

Any Compound I 25-80 Dimethylformamide 20 Xylene 30 Methoxyethyl acetate 10 Polyoxyethylene nonylphenyl ether 15 Example 49 (solution):

Any Compound I 3 Methylnaphthalene 30 Kerosene 5O Methyl isobutyl ketone Tributyl phosphate 7 Example 50 (bait):

Any Compound I 1 Fish meal 10 Bran 50 Sawdust 20 Beef tallow 4 Starch What is claimed is: 1. An organophosphorus compound of the formula z Y 0R wherein X is H, halogen or alkyl of up to 4 carbon atoms,

Z is carbonyl, alkylidene of up to 6 carbon atoms,

benzylidene or cyclohexylidene, Y is O or S, -Y is O- or CH Y in which --Y is O or S- directly bound to ll/ l) R is methyl or ethyl, and

R is methoxy, ethoxy or phenyl.

2. The compound 0,0-diethy1 O-(2,4-dioxo-2,3-dihydro-4H-1,3-benzoxazin-3-yl) phosphorothioate.

3. The compound diethyl (2,4-dioxo-2,3-dihydro-4H- 1,3-benzoxazin-3-yl) phosphate.

4. The compound 0,0-dimethyl S-[(2,4-dioxo-2,3-dihydro-4H 1,3 benzoxazin 3 yl)methyl] phosphorodithioate.

5. The compound 0,0-diethyl S-[(2,4-dioxo-2,3-dihydro-4H-1,3-benzoxazin-3-yl)methyl] phosphorodithioate.

6. The compound 0,0-diethyl O-[(6-bromo-2,4-dioxo- 2,3-dihydro-4H-1,3-benzoxazin-3-yl)methyl] phosphorothioate.

7. The compound 0,0-diethyl O-(8-methyl-2,4-dioxo- 2,3-dihydro-4H-1,3-benzoxazin-3-yl) phosphorothioate.

8. The compound 0,0-dimethyl O-(2-isopropyl-4-ox0- 2,3-dihydro-4H-l,3-benzoxazin-3-yl) phosphorothioate.

9. The compound 0,0-diethyl O-(2-phenyl-4-oxo-2,3- dihydro-4H-l,3-benzoxazin-3-yl) phosphorothioate.

10. The compound 0,0-diethyl O-(2-methyl-4-oxo-2,3- dihydr0-4H-1,3-benzoxazin-3-yl) phosphorothioate.

11. The compound 0,0-diethyl O-(2-ethyl-4-oxo-2,3- dihydro-4H-1,3-benzoxazin-3-yl) phosphorothioate.

12. The compound 0,0-diethyl O-(2-isopropyl-4-oxo- 2,3-dihydro-4H-l ,3-benzoxazin-3-yl) phosphorothioate.

13. The compound 0,0-diethyl O-(2-butyl-4-oxo-2,3- dihydro-4H-l,3-benzoxazin-3-yl) phosphorothioate.

References Cited UNITED STATES PATENTS 4/1955 Morris et al 260-244 7/1961 McConnell et a]. 260244 OTHER REFERENCES HENRY R. JILES, Primary Examiner NATALIE TROUSOF, Assistant Examiner US. Cl. X.R. 424-200 

